The clinical manifestations of oral phosphorus poisoning are classically described in three stages. The initial effects may be delayed for a few hours, and the degree of delay depends on the dose. During the first phase, patients experience vomiting, hematemesis, and abdominal pain, with hypotension and death occurring within 24 hours after large ingestions.7 During the second stage, there is transient resolution of the toxic effects. During the third stage, the patient develops hepatic injury with coagulopathy and jaundice and acute kidney injury with oliguria and uremia. Mental status changes and seizures (independent of electrolyte changes) are also reported. However, clinical experience demonstrates that three distinct phases are the exception rather than the rule, with significant overlap or absence of the “quiescent” second stage and death potentially occurring within hours of ingestion.6,15 In the first 6 hours postexposure, poor prognostic signs include altered sensorium, cyanosis, hypotension, metabolic acidosis, elevated prothrombin time, and hypoglycemia.6 Survival to 3 days serves as a good prognostic sign. However, deaths occur later in the clinical course.7 Recovery usually occurs over 1 to 2 weeks.
Initial symptoms after ingestion of phosphorus include nausea, vomiting, and abdominal pain. Both diarrhea and constipation are reported but are much less common. The breath and vomitus are sometimes described as having a garlic or musty sweet odor. The vomitus and diarrhea are sometimes luminescent and smoking, but this specific finding occurs infrequently. The smoking material is caused by the combustion of phosphorus upon its reexposure to air after being eliminated from the GI tract. Phosphorus causes an inflammatory injury to the GI tract characterized by local hemorrhage and hematemesis, but generally perforation does not occur. Massive GI bleeding may occur later in the clinical course, particularly when hepatic failure and coagulopathy are present.10
In a rat model of dermal burns from phosphorus, an initial diuresis occurs followed by acute kidney injury manifested by hyperkalemia, hyponatremia, and hyperphosphatemia.1 Renal cell swelling and necrosis with vacuolar degeneration of proximal convoluted tubules was also observed.1 Poisoned patients demonstrated an increase in urinary white and red blood cells with casts and proteinuria.3 In humans, acute kidney injury from phosphorus is most likely acute tubular necrosis resulting from hypotension, salt and water depletion, and a direct toxic effect.7
Significant electrolyte disturbances may result from both ingestion and dermal absorption of phosphorus. Hypocalcemia is common, but hypercalcemia is also occasionally reported.13 Hyperphosphatemia may accompany the hypocalcemia but is not universal and can occur at any time in the clinical course.3 The hyperphosphatemia is partially due to the conversion of absorbed phosphorus to phosphate. In an animal model, those that died had increased concentrations of phosphorus, decreased concentrations of calcium, and hyperkalemia as early as one hour postexposure.2 Hyperkalemia is occasionally reported in humans and may be secondary to tissue injury and acute kidney injury.1 The electrolyte disturbances are likely a leading cause of early mortality from phosphorus.
Death within 24 hours of the ingestion is likely the result of cardiovascular collapse. One series of 41 patients who attempted suicide demonstrated a variety of initial electrocardiographic (ECG) abnormalities. T wave changes predominated in 24 patients, and there were also two cases of ventricular fibrillation. An increasing number of ECG abnormalities occurred in patients with larger ingestions, although the electrolyte abnormalities were not described in many patients.7 An animal model of phosphorus exposure demonstrated prolonged QT interval and ST segment changes along with electrolyte abnormalities, suggesting that many of the ECG changes might be due to electrolyte abnormalities.2 A small study of phosphorus exposure in rats observed a decrease in amino acid uptake in myocytes suggesting a direct toxic effect. Human autopsies of several poisoned patients demonstrated fatty degeneration of the myocardium and vacuolated cytoplasm many hours postingestion.19
Phosphorus is a potent hepatotoxin. Increase in prothrombin time, hyperbilirubinemia, and hypoglycemia usually occur within 3 days, with earlier signs of hepatic failure such as jaundice and coagulopathy indicative of a poor prognosis.7,14 The increase in hepatic aminotransferases occurs over several days, usually peaking at or below 1000 IU/L and almost invariably less than 3000 IU/L.10 Other biochemical effects demonstrated by experimental phosphorus toxicity include an increase in glucose-6-phosphate activity and impairment of triglyceride metabolism and protein synthesis. When death occurs after several days (as opposed to within 24 hours), hepatic injury is usually implicated. If survival occurs, the hepatic damage usually resolves over several months, although persistent periportal fibrosis is reported.14
With absorption of sufficient quantities, phosphorus causes a dose-related zone 1 or periportal hepatic injury, in contrast to the centrilobular pattern (zone 3) that occurs with other hepatotoxins, such as acetaminophen and carbon tetrachloride (Chap. 23). Fatty degenerative changes and fatty infiltrates are also observed within 6 hours of ingestion.6 Other histological changes include acute necrosis with large vacuoles and inflammatory changes. Electron microscopy in a rat model demonstrated an increase in the rough endoplasmic reticulum and an increase in the cytoplasmic fat without initial mitochondrial or nuclear injury.11 Although the early pathological effects appear to be predominantly cytoplasmic, the formation of nuclear vacuoles can occur.14
Central nervous system effects include headache, altered mental status, coma, and rarely seizures. The altered mental status is probably due partially to the presence of other organ dysfunction and shock; one example of the former is the encephalopathy secondary to hepatic injury. Patients with initial alterations in mental status or coma have an increased mortality rate independent of the presence of any electrolyte abnormalities.15
Dermal phosphorus exposure causes extensive burns, and this occurs most frequently in the military setting. The burns are described as emitting a garlic odor and displaying a yellow color that fluoresces under ultraviolet light. Necrosis of the wounds is common when wound decontamination is incomplete. Depending on the release conditions, white phosphorus can be a solid or liquid. Liquid white phosphorus splatters and can penetrate clothing; burning clothing commonly exacerbates the burn area.13,16 Dermal penetration may be partially due to its lipophilicity and a compromised dermal barrier caused by the burn injury. The smoke produced by burning white phosphorus contains phosphorus pentoxide and is irritating to the conjunctiva and mucosa of the oropharynx and lungs.
Following a large burn, systemic illness manifested by electrolyte, cardiovascular, and hepatic abnormalities may result from absorbed phosphorus.1,2 A 12% to 15% body surface area burn in a rat was lethal 50% of the time; human morbidity from large skin burns is similarly high. Rats with dermal burns from phosphorus subsequently developed kidney and liver injury. Healing time from phosphorus burns is prolonged when compared with thermal burns.7